[Karyometry of BBN-induced precancerosis of the urothelium : An experimental analysis]. / Karyometrie BBN-induzierter Präkanzerosen des Urothels : Eine experimentelle Analyse.

BACKGROUND: The morphology of experimental precancerous lesions of the urinary bladder has been interpreted quite differently by various authors. OBJECTIVES: The aim of this investigation was to quantify these lesions by karyometry and, thus, to gain a more reliable understanding of the process. MATERIALS AND METHODS: A total of 60 Wistar rats were fed with N­butyl-N-(4-hydroxybutyl)nitrosamine (BBN) at a concentration of 0.05 % in their drinking water to induce preneoplastic changes of the urothelium. After the second week of BBN exposition, 6 animals were killed every 2 weeks up to week 20. Smears of the scraped off urothelium of 3 urinary bladders of each group were analyzed cytologically and karyometrically. RESULTS: BBN exposition led to statistically significant changes of the karyometric values using the χ2 test to differentiate the control animals from the ones that had ingested BBN and the 2­week groups from each other. These changes consisted mainly in significant deviations of the size of the nuclear area within the different groups. CONCLUSION: Morphological and karyometrical analysis showed that biologically relevant stages in the development of chemically induced urothelial precancerous lesions could be realized much earlier than had been assumed in recent publications. Karyometric analysis offered a valid basis to describe the early morphologic alterations of carcinogenesis.

Schistosoma japonicum infection and rectal carcinoid tumour: underreported coincidence or neglected association?

Schistosoma japonicum infection associated with a rectal carcinoid in an asymptomatic 44-year-old female from the Philippines is described. A systematic review of the literature could not identify similar reports, suggesting a rare coincidence. However, epidemiological data on the frequency of both conditions as well as published results of a colorectal screening programme from China indicate that underreporting of this concurrence is likely. Moreover, several studies suggest a causal link between schistosomiasis caused by S. japonicum and more common gastrointestinal malignancies such as colorectal carcinoma. Hence the presented case and the apparent neglect of this observation in the current literature allow speculation on a role of S. japonicum in the pathogenesis of rare gastrointestinal neoplasms such as carcinoid tumours as well. Future reports on similar observations could help to determine the need for systematic investigations and are strongly encouraged.

[Phenprocoumon-induced liver failure]. / Phenprocoumon-induziertes Leberversagen.

HISTORY: A 61-year-old woman was referred because of painless jaundice, laboratory tests having indicated hepatitis with impaired liver functions. For the past two years she had been taking phenprocoumon because she had atrial fibrillation. INVESTIGATIONS: Serological tests largely excluded infectious, autoimmune or metabolic etiology, so that the diagnosis of drug-induced hepatic disease was made. Liver biopsy showed necrotic liver cells and mild inflammatory reaction. TREATMENT AND COURSE: A perforating duodenal ulcer required urgent surgical intervention, after which liver functions further deteriorated. The patient having refused liver transplantation she was treated symptomatically (oral vitamin K. lactulose, diuretics), phenprocoumon was discontinued and her condition slowly improved. She was discharged after two months. At subsequent examination she was symptom-free, the INR was 1.41, transaminases were normal and ultrasound merely showed a slightly inhomogeneous internal structure. CONCLUSION: Phenprocoumon can cause liver damage even when the drug has been taken for prolonged periods without any problems. A careful history about previously administered drugs should be taken in any case of hepatitis of uncertain etiology.

[Severe cholestasis with kidney failure from anabolic steroids in a body builder]. / Schwere Cholestase mit Nierenversagen durch Anabolika bei einem Bodybuilder.

HISTORY AND ADMISSION FINDINGS: A 28-year-old body builder was admitted because of jaundice. For 80 days, until 3 weeks before hospitalization, he had been taking moderately high doses of anabolic steroids: metandienone (methandienone), 10-50 mg daily by mouth, and stanozolol, 50 mg intramuscularly every other day. Physical examination was unremarkable except for yellow discoloration of the skin and sclerae. INVESTIGATIONS: Bilirubin concentration was raised to 4.5 mg/dl, cholestasis enzymes were normal, while transaminase activities were raised. Liver biopsy was compatible with cholestasis induced by anabolic steroids. TREATMENT AND COURSE: Although the steroids had been discontinued, the patient's general condition deteriorated over 7 weeks. Serum bilirubin rose up to a maximum of 77.9 mg/dl. In addition renal failure developed with a creatinine concentration of 4.2 mg/dl. The patient's state improved simultaneously with the administration of ursodeoxycholic acid and the biochemical values gradually reached normal levels after several weeks. CONCLUSION: Anabolic steroids can cause severe cholestasis and acute renal failure. In this case there was a notable temporal coincidence between the administration of ursodeoxycholic acid and the marked clinical improvement.

Oral budesonide and ursodeoxycholic acid for treatment of primary biliary cirrhosis: results of a prospective double-blind trial.

BACKGROUND & AIMS: Ursodeoxycholic acid (UDCA) is used for treatment of primary biliary cirrhosis. Previous studies showed that, compared with UDCA monotherapy, bile salts plus prednisolone had no further effect on laboratory data but improved liver histology. Thirty percent of these patients had prednisolone-related side effects. Budesonide is a glucocorticoid with a high receptor affinity and a high first-pass metabolism. In this study we investigated whether budesonide and UDCA are superior to UDCA monotherapy. METHODS: A 2-year prospective, controlled double-blind trial was performed. Twenty patients (mainly with early-stage disease) were treated with UDCA at a dose of 10-15 mg/kg daily in addition to 3 mg budesonide 3 times daily (group A), and 19 patients (1 dropped out for personal reasons) were treated with UDCA plus placebo (group B). Liver biopsy specimens were taken before, after 12 months, and at the end of study. Glucose tolerance tests, serum cortisol levels, and adrenocorticotropin-stimulated cortisol secretion were assessed at regular intervals. Bone mass density was measured by dual-energy photon absorptiometry. RESULTS: Compared with pretreatment values, liver enzyme and immunoglobulin M and G levels decreased significantly in both groups. Improvement in group A was significantly more pronounced (P < 0.05) than in group B. Titers of antimitochondrial antibodies did not change. In group A, the point score of liver histology improved by 30.3%; in group B, it deteriorated by 3.5% (P < 0.001). Changes in bone mineral density after 2 years were -1.747% in group A and -0.983% in group B (P = 0.43). Budesonide had little influence on the hypothalamic-pituitary-adrenal axis. One patient in group A had budesonide-related side effects; in 3 patients in group B, complications of liver disease developed. CONCLUSIONS: Combination therapy with UDCA and budesonide is superior to UDCA and placebo.

[Miliary pneumonia after the intravesical BCG therapy of a superficial urothelial carcinoma of the bladder]. / Miliare Pneumonie nach intravesikaler BCG-Therapie eines oberflächlichen Urothelkarzinoms der Harnblase.

HISTORY AND ADMISSION FINDINGS: A multilocular superficial epithelial carcinoma (T1G3) and carcinoma in situ (Cis G3) of the bladder were resected transurethrally followed by intravesical instillation of BCG. The initial cycle of BCG administration had been free of complication, but then high fever, fatigue, cough and dyspnoea had developed with subsequent BCG maintenance treatment. Physical examination on admission revealed fever, clearly reduced general condition, and increased breath sounds with fine rales in the upper and middle lobes. INVESTIGATIONS: A clearly raised erythrocyte sedimentation rate (86 mm/h) and a CRP level at the upper limit of normal (13.6 mg/dl) indicated marked inflammatory reaction. The chest radiogram showed diffuse miliary opacities. Mycobacteria were not demonstrated in either gastric juice or bronchial secretion. TREATMENT AND COURSE: As BCG-induced miliary pneumonia was diagnosed, triple tuberculostatic treatment was commenced (ethambutol, 1200 mg/d; rifampicin, 600 mg/d; isoniazid, 300 mg/d). Nonetheless his condition deteriorated further. When prednisolone, 40 mg/d was added the symptoms improved rapidly. The tuberculostatic drugs were continued for 6 months. All symptoms had disappeared after 4 months. CONCLUSION: Miliary pneumonia is a rare complication of intravesical BCG installation of a superficial bladder cancer. As living bacteria cannot be excluded as the cause, triple tuberculostatic treatment must be started at once. If this fails to bring about improvement, additional steroid medication is recommended.

[Necrotizing hepatitis after taking herbal remedies]. / Nekrotisierende Hepatitis nach Einnahme pflanzlicher Heilmittel.

HISTORY AND CLINICAL FINDINGS: Two unrelated women, aged 39 and 42 years, had been admitted (at different times) to hospital because of "recurrence of an aetiologically uncertain acute hepatitis". Both patients had a history of acute hepatitis with GPT concentration of 796 and 755 U/l, respectively. Each of them had experienced recurrences of hepatitis, each of them preceded by taking herbal remedies as alternative medication, containing kava or common (or lesser) celandine, respectively. In each patient physical examination had been unremarkable. INVESTIGATIONS: Maximal values of GPT in the two patients were 422 and 350 U/l, respectively. Viral, autoimmune and metabolic causes of the hepatitis were excluded. In each of them liver biopsy revealed the picture of acute necrotizing hepatitis. DIAGNOSIS, TREATMENT AND COURSE: As it was suspected that the hepatitis was medication-induced, the intake of the mentioned herbal preparations was stopped. The liver function tests quickly became normal. CONCLUSION: In view of the rapid response to their withdrawal, a causal connection between intake of the herbal preparations and the recurrences of acute hepatitis is the most likely explanation in both cases.

Melanocytic neuroendocrine carcinoma of the thymus.

A neuroendocrine carcinoma of the thymus with an ectopic adrenocorticotropic hormone (ACTH) syndrome and melanocytic differentiation is described. ACTH, neuron-specific enolase (NSE) and S-100 protein were identified in the tumor by immunocytochemistry. Neurosecretory granules and melanosomes could be demonstrated in different cell populations by electronmicroscopy. The clinicopathologic findings are presented. The literature is briefly discussed.

[Intestinal lipodystrophy (M. Whipple). Synopsis of radiology, endoscopy and histology]. / Intestinale Lipodystrophie (M. Whipple). Synopsis von Radiologie, Endoskopie und Histologie.

The case of a 48 years old man with intestinal lipodystrophy (Whipple's disease) is clinically, roentgenologically, endoscopically and histologically documented. The diagnosis was established by endoscopic biopsy and laparatomy. The patho-histologic changes of the mucosa of the proximal small bowel are pathognomonic. Roentgenologically the characteristic mucosal and lymphadenoid changes can be demonstrated as well as the extent of the process.

Intravesical single and combination therapy in superficial bladder cancer. An experimental study.

In this animal experiment it was investigated if intravesical combination therapy is superior to single drug therapy to reduce the growth of N-butyl-N(4-hydroxybutyl)-nitrosamine (BBN)-induced bladder carcinomas in the rat. The evaluation of the histological data gave the following results: intravesical instillation of cytostatic drugs in concentrations similar to that used in man reduce the growth of BBN-induced tumors. The effectiveness of mitomycin C or adriamycin alone is similar to that of alternative administration of mitomycin C and adriamycin.

[Frequency of recurrences and tumor progression on superficial bladder carcinoma (author's transl)]. / Rezidivhäufigkeit und Tumorprogression superficialer Harnblasenkarzinome.

A retrospective study with an adequate follow-up of three years or longer of 315 superficial transitional cell carcinomas (Ta--T2) is reported. Patients had transurethral resection in 80% and open excision or resection in 20% for cure or control. It is demonstrated, that in addition to the grade and the stage of the tumor, multifocal tumor growth and whether it is a primary or recurrent tumor influence the frequency of recurrences and the tumor progression. The overall percentage of recurrences after resection of Ta, T1 and T2 tumors within three years is 60%. A primary tumor recurs in 45%, the first recurrence in 84%, solitary tumors in 46% and multifocal tumors in 73%. Tumor progression is observed in solitary tumors in 24%, in multifocal tumors in 44%, in primary and recurrent Ta and primary T1 tumors in 20 to 25%, in recurrent T1 tumors in 56%. Therefore, when planning therapy, stage, grade, multifocal tumor growth and whether it is a primary or recurrent tumor should be considered. Ta tumors can be treated sufficiently by transurethral resection, even in case of several recurrences; more aggressive therapy should be considered, when multifocal or recurrent T1 or T2 tumors recur again as invasive carcinomas.

[Clinical diagnosis of bladder cancer]. / Klinische Diagnostik beim Blasenkarzinom.

The minimum requirements of the International Union against Cancer (UICC) to assess the TNM-classification of urothelial bladder cancer include since 1978 the clinical examination, urography, cystoscopy, bimanual palpation under anesthesia and biopsy or transurethral resection of the tumor. The single biopsy of the tumor should be supplemented by multiple biopsies of all bladder walls in combination with the resection of the tumor to diagnose multifocal tumor growth. The exfoliative urinary cytology should be included in the routine diagnostic regimen: cytology is helpful in detection of severe dysplasia and controls the histologically determined grade of the tumor. In selected cases computer tomography improves the accuracy of clinical evaluation of the depth of tumor infiltration. In our hands the lymphangiography can not assess the regional lymph node metastases: therefore, the staging operation is recommended before radical cystectomy is performed.

Scanning and transmission electron microscopic observations of the cloacal epithelia of the domestic fowl.

The epithela of the three divisions (coprodaeum, urodaeum, proctodaeum) of the cloaca of the hen, and of the excretory ducts (colon, ureter, vagina) which join the divisions, are described using light microscopy, and scanning and transmission electron microscopy. Each region of the cloaca has its typical epithelium. Special attention is focussed in this study on the boundaries between the different epithelia. The coprodaeal epithelium does not differ considerably from that of the colon; a transitional zone is not visible. Distinct border zones, however, are observed between the other regions (ureter--urodaeum; vagina--urodaeum and proctodaeum; urodaeum--proctodaeum; proctodaeum--cutis). Although the vaginal opening is generally thought to lie in the urodaeum, our investigations show that at the vaginal opening into the cloaca the ciliated epithelium changes, on one border to a secretory epithelium characteristic of the urodaeum and on the other border to that characteristic of the proctodaeum. These observations are discussed in relation to functional aspects.